Unichiral 2-(2 '-Pyrrolidinyl)-1,4-benzodioxanes: the 2R,2 ' S Diastereomer of the N-Methyl-7-hydroxy Analogue Is a Potent alpha 4 beta 2-and alpha 6 beta 2-Nicotinic Acetylcholine Receptor Partial Agonist (Articolo in rivista)

Type
Label
  • Unichiral 2-(2 '-Pyrrolidinyl)-1,4-benzodioxanes: the 2R,2 ' S Diastereomer of the N-Methyl-7-hydroxy Analogue Is a Potent alpha 4 beta 2-and alpha 6 beta 2-Nicotinic Acetylcholine Receptor Partial Agonist (Articolo in rivista) (literal)
Anno
  • 2011-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1021/jm200937t (literal)
Alternative label
  • Bolchi, Cristiano; Gotti, Cecilia; Binda, Matteo; Fumagalli, Laura; Pucci, Luca; Pistillo, Francesco; Vistoli, Giulio; Valoti, Ermanno; Pallavicini, Marco (2011)
    Unichiral 2-(2 '-Pyrrolidinyl)-1,4-benzodioxanes: the 2R,2 ' S Diastereomer of the N-Methyl-7-hydroxy Analogue Is a Potent alpha 4 beta 2-and alpha 6 beta 2-Nicotinic Acetylcholine Receptor Partial Agonist
    in Journal of medicinal chemistry
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Bolchi, Cristiano; Gotti, Cecilia; Binda, Matteo; Fumagalli, Laura; Pucci, Luca; Pistillo, Francesco; Vistoli, Giulio; Valoti, Ermanno; Pallavicini, Marco (literal)
Pagina inizio
  • 7588 (literal)
Pagina fine
  • 7601 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 54 (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali
  • 14 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
  • 21 (literal)
Note
  • ISI Web of Science (WOS) (literal)
  • ISI Web of Science (WoS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • University of Milan; Consiglio Nazionale delle Ricerche (CNR); Neuromed IRCCS (literal)
Titolo
  • Unichiral 2-(2 '-Pyrrolidinyl)-1,4-benzodioxanes: the 2R,2 ' S Diastereomer of the N-Methyl-7-hydroxy Analogue Is a Potent alpha 4 beta 2-and alpha 6 beta 2-Nicotinic Acetylcholine Receptor Partial Agonist (literal)
Abstract
  • A series of unichiral 7-substituted 2-(1'-methyl-2'pyrrolidinyl)-1,4-benzodioxanes were synthesized and tested for the affinity for the alpha 4 beta 2 and alpha 7 central nicotinic receptors; the 2R,2'S diastereomer of the 7-OH analogue [(R,S)-7], unique in the series, has a high alpha 4 beta 2 affinity (12nM K(i)). N-Demethylation and configuration inversion of the stereocenters greatly weaken its alpha 4 beta 2 affinity, confirming that such a rigid molecule can be considered a new template for alpha 4 beta 2 ligands. Docking analysis showed how (R,S)-7 is capable of strongly and specifically interacting with the amino acidic counterpart of the alpha 4 beta 2 receptor binding site. Further pharmacological characterization demonstrated that (R,S)-7 also has a high affinity for the alpha 6 beta 2 receptor, and in vitro functional tests indicated that it is a potent alpha 4 beta 2 and alpha 6 beta 2 partial agonist, with modest affinity and potency for the alpha 3 beta 4 receptor. Comparison with varenicline, a well-known nicotinic partial agonist used as a smoking cessation aid, interestingly reveals similar nicotinoid profiles. (literal)
Prodotto di
Autore CNR

Incoming links:


Prodotto
Autore CNR di
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi
data.CNR.it